Metal-Free Formal Inverse-Electron-Demand Diels-Alder Reaction Of 1,2-diazines With Ynamides

Ynamide is a kind of spcial species of ynamines,with acetylene bond directly linked to amide functional group.This unique p-?conjugated system controlled by electron-withdrawing acyl group directly changes reactivities of the two acetylene carbons.The?-site carbon atom has electrophilicity while?-site carbon atom has nucleophilicity.Induced by electron-withdrawing-group acyl,the lone pair electrons of nitrogen atom can delocalize to the acyl group,which enable lower the electronic cloud density of acetylene bond and produce a good balance between chemoreactivity and stability.Compared with the common alkynes,ynamides have better applicatio-nal value and regioselectivity.In addition,ynamides have better thermodynamic stability and chemoreactivity than ynamines.Ynamides are significant innovations based on the structures of ynamines,whose major specific structural types include oxazolidinone,imidazolidinone,lactam and acyclic sulfonamides.In this thesis,the research work of 2-aminonaphthalenes and 2-aminoanthrenes compounds synthesized by inverse-electron-demand Diels-Alder reaction involving non-metal catalyst and ynamides is introduced.This research work is divided into three chapters,the first chater presents the synthetic methods and applications of ynamides,while the second chapter describes the applications in[4+2]cycloaddition of azines.The third chapter introduces a new method for the“Metal-Free Formal Inverse-Electron-Demand Diels-Alder Reaction of 1,2-Diazines with Ynamides”to synthesize 2-aminonaphtha-lenes and 2-aminoanthrenes compounds.Both 2-aminonaphthalenes and 2-aminoanthrenes compounds are important intermediates for the synthesis of pharmacodynamic molecules.For example,neuroprotective drug TVA-20 synthesized by 2-aminonaphthalene according to combination principles of medicinal chemistry,can be used for the treatment of stroke,senile dementia,Parkinson's disease and brain trauma sequelae et.The compound 2-?2-anthryl?-amino-4-methylthiazole-5-carboxylic acid ethyl ester,which belongs to thiazole-scaffold analogues synthesized by the 2-aminoanthrene,is expect-ed to be developed as a drug candidate molecule for the treatment of rheumatoid arthritis by suppressing the bioactivity of human dihedroorotate dehydrogenase.Therefore,to discover and develop a new and efficient method for constructing2-aminonaphthalenes and 2-aminoanthrenes compounds bear vital practical values.This paper describes a new method for the inverse-electron-demand Diels-Alder reaction of 1,2-diazines with ynamides catalyzed by trifluoromethanesulfonic anhydride to synthesize 2-aminonaphthalenes and 2-aminoanthrenes compounds.Not only is this new method an importment supplement to this field,but also it develops a novel approach for synthesizing 2-aminonaphthalenes or 2-aminoanthrenes compounds.In addition,this reaction survives cascade procedures including[4+2]cyclization/reverse[4+2]ring-opening release N₂/aromatization,with features of convenient operation,high regioselectivity,excellent yields and good substrates suitability.